Individuals with LH/CG-R carrying activating mutations develop familial male-limited precocious puberty and often have behavioral problems. The behavioral problem seen in patients with FMPP patients may be related to dysfunction of brain cells caused by the mutated receptor. Recent studies demonstrated human chorionic gonadotropin (hCG) and its receptor (LH/CG-R) may have nongonadal functions which could be important physiologically. In the nervous system LH/CG-R is expressed in the mammalian brain in a temporal and spatial pattern. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. However, the function of hCG and its receptor in the nervous system remains unclear. [unreadable] [unreadable] To understand the role of hCG and its receptor in the development of the mammalian nervous system, we studied the effect of the transgenes on the differentiation of the bipotent cell line, PC12, derived from rat adrenal pheochromocytoma. Our studies showed that the differentiation effect of hCG was ligand dose- and time-dependent. Both the extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (MAPK) were indispensable for the differentiation process. In addition, the Phospholipase C (PLC) pathway was partially involved in hCG induced PC12 differentiation. These findings imply a potential role of hCG/LH and LH/CG-R in the neurogenesis of the mammalian nervous system. Our studies also suggested that hCG promotes myelination through inducing myelin protein zero (P0) expression. the findings of these studies suggest that hCG/LH and its receptor participate in the development and maintenance of the mammalian nervous system. hCG may be a potential regeneration drug for future treatment of acute neural injuries or neurodegenerative disorders.